Mendes, T. A. d. O. | bioRxiv Science

bioRxiv2023

First Genome-Scale Metabolic Modeling of Brucella abortus Predicts Pathogen Gene Essentiality and New Drug Target

Bovine brucellosis, a globally widespread disease, imposes substantial economic burdens on livestock production. The pathogen, Brucella abortus, has a particular affinity for infecting cattle and can also impact humans, potentially posing a public health risk in regions where the disease persists. To gain a deeper understanding of the pathogens biology and its interactions with the host, Pathogen-specific Genome-Scale Metabolic Models offer valuable insights. They aid in identifying novel pharmacological targets and biomarkers, which can inform innovative brucellosis control strategies. In this study, we developed and validated the first Genome-Scale Metabolic Model of B. abortus 2308, named iBP932, encompassing 932 genes, 1,140 reactions, and 999 metabolites. Furthermore, iBP932 capability to predict potential drug targets was demonstrated.

systems biology↗

bioRxiv2021

Discovery of 10,828 new putative human immunoglobulin heavy chain IGHV variants

The correct identification of immunoglobulin alleles in genome sequences is a challenge. Nevertheless, it can assist in the study of several human diseases associated with the antibody repertoire and in the development of new therapies using antibody engineering techniques. The advent of next-generation sequencing of human genomes and antibody repertoires enabled the development of several tools for the mapping and identification of new immunoglobulin (Ig) alleles. Some of these tools use 1,000 Genomes (G1K) data for new Ig alleles discovery. However, genome data from G1K present low coverage and variant call problems. Here, a computational screen of immunoglobulin alleles was carried out in the Genome Aggregation Database (gnomAD), the largest high-quality catalogue of variation from 125,748 exomes and 15,708 human genomes. A total of 10,909 putative IGHV alleles were identified, in which 10,828 of them are new and 2,024 appear at least in 6 different alleles from genomes/exomes. The IGHV2-70 was the IGHV gene segment with the largest number of variants described. The majority of the variants were found in the framework 3 and most of them are missense. Interestingly, a large number of variants were found to be population exclusive. A database integrated with a web platform was created (YGL-DB) to store and make accessible the likely new variants found. This available data can help the scientific community to validate new IGHV variants as well as it can shed light on the importance of variants in disease development and immunization protocols.

immunology↗